Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS)
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Multi-functional scaling is a mechanistic framework to design integrated microphysiological systems for pharmacological applications.
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It is difficult to balance competing key functional indices in multi-OoC setups; for a gut-liver system, a perfusion rate chosen for the gut to yield proper metabolic rates might result in drug exposure times in the liver that are too short.
“it has proven difficult to balance competing key indices in multi-OoC setups; for a gut–liver system139, for example, a perfusion rate chosen for the gut to yield proper metabolic rates might result in drug exposure times in the liver that are too short”
From Human disease models in drug development (2023) · cites this paper as [139]
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Experimental — accuracy not yet measuredThese considerations ensure correct translation of key functional indices from the model to in vivo conditions.
“These considerations ensure the correct translation of the key functional indices from the model to in vivo conditions139”
From Human disease models in drug development (2023) · cites this paper as [139]
The Introduction describes functional scaling as a way to recapitulate selected in vivo functions, and the Results and Discussion report that multi-functional scaling captured drug-exposure times similar to those in vivo. But the paper does not say these considerations ensure correct translation of functional indices generally; it cautions that translation depends on adequately capturing in vivo physiology. The provided passages have section labels but no page numbers. (LLM, conf=0.84)
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References 78 · Cited by 72
Research works printed but not linked: 7
- [27]ICRP Annals of the ICRP 2002 32 5 265 14506981
- [35]Borgstroem L Johansson C Larsson H Lenander R J Pharmacokinet Biopharm 1981 9 419 429 7310641
- [41]Wooding-Scott RA Smalley J Visco J Slaughter RL Br J Clin Pharmac 1988 26 415 421 PMC1386563 3190991
- [42]McFayden ML Folb PI Miller R Marks IN Moshal MG Eur J Clin Pharmacol 1983 24 441 447 6305671
- [46]Tassaneeyakul W Kittiwattanagul K Vannaprasaht S Kampan J Tawalee A Puapairoj P Tiamkao S Juthagridsada S Kukongviriyapan V Tassaneeyakul W J Pharm Pharm Sci 2005 8 47 53 15946597
- [54]Korting-Schäfer M Bach N Knauf H Mutschler E Eur J Clin Pharmacol 1984 26 125 127 6714285
- [69]Obach RS Drug Metab Dispos 1997 25 1359 1369 9394025
- Authors
- Maass, C., Stokes, C. L., Griffith, L. G., & Cirit, M.
- Affiliations
- Massachusetts Institute of Technology (US)
- Stokes Consulting
- Corresponding author
- Cirit, Murat
- Venue
- Integrative Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017
- Volume
- 9
- Issue
- 4
- Pages
- 290-302
- ISSN
- 1757-9694 (ISSN-L)
- 1757-9708
- PMC
- PMC5729907
- OpenAlex
- W2594151080
- Cited by
- 72
- References
- 78
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 12 · 2019: 13 · 2018: 11 · 2017: 5
- FWCI
- 5.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Integrative Biology (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Defense Advanced Research Projects Agency (W911NF-12-2-0039)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- microphysiological systems, scaling methods, mechanistic modeling, allometric scaling, drug exposure, pharmacokinetics, pharmacodynamics, drug absorption and metabolism, exposure-response relationship
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Humans, Intestinal Mucosa, Intestines, Kidney, Liver, Models, Biological, Pharmacokinetics, Cell Culture Techniques, Translational Research, Biomedical
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